CUA: Adrenal Mass (2011)

See Original Guideline

See Disorders of Adrenals Chapter Notes

Incidental adrenal mass

• Definition of incidental adrenal mass: a serendipitously discovered adrenal lesion >1cm on radiologic examination done for reasons other than to investigate for primary adrenal disease
• Adrenal incidentaloma is excluded in patients with:
  • Known malignancy or high suspicion of malignant processes [since adrenal mass has high likelihood of being a metastatic deposit]
  • Clinically overt disease

Diagnosis and Evaluation

• See Figure 1 from Original Guideline
  • Note: figure may contain typographic errors with symbols for APW/RPW since Campbell’s states: An absolute percent washout (comparing noncontrast values with 15-minute postcontrast density values - ([Enhanced − delayed]/[Enhanced − unenhanced] × 100%) > 60%, or a relative percent washout (RPW) (comparing arterial phase density measurements with 15-minute postcontrast density values - ([Enhanced − delayed]/ Enhanced × 100%)) > 40% on delayed (washout) imaging, is indicative of adenoma
• All incidental adrenal masses (excluding myelolipomas, hemorrhages, and cysts) initially require a comprehensive workup, including thorough clinical, radiologic and hormonal evaluations to distinguish benign from malignant processes, as well as non-functioning from hyperfunctioning tumours.
• History and physical exam
  • Evaluate for overt signs and symptoms of primary adrenal disease; however, most patients with adrenal incidentalomas are asymptomatic
• Labs
  • Hormonal evaluation
    • Hypercortisolism is assessed by overnight 1 mg dexamethasone suppression test (DST, sensitivity: 85-90 specificity: 95-99). Consideration can be given to using the 24-hour urine free cortisol (UFC, sensitivity: 80-98 specificity: 45-98) for screening with the low dose DST used to differentiate Cushing’s from subclinical Cushing’s syndrome if the cortisol level on the 24-hour test is elevated. A subset of patients with Cushing’s syndrome may have normal UFC (false-negative). For further details on hypercortisolism testing: https://www.ncbi.nlm.nih.gov/pubmed/31069279
    • Presence of pheochromocytoma is assessed by 24-hour urine metanephrines and catecholamines
      • Fractionated plasma metanephrines is a newer test that may be more sensitive, but less specific. As such, its use should be reserved for confirmatory testing as opposed to primary screening. Plasma metanephrine testing may not be widely available outside select centres, therefore 24-hour urinary metanephrines is suggested for initial screening.
    • Hypertensive patients with adrenal incidentalomas should be assessed for hyperaldosteronism (HA).
      • Traditionally, HA has been clinically associated with hypertension and hypokalemia, however, normokalemia occurs in up to 50% of patients with HA.
      • The best screening test is upright plasma aldosterone concentration to plasma renin ratio (ARR).
        • Mineralocorticoid receptor blockers (e.g. spironolactone) and some diuretics, particularly potassium sparing diuretics (e.g. amiloride, triamterene) and potassium wasting diuretics (e.g. furosemide, HCTZ, indapamide), should be discontinued at least 4 weeks prior to the ARR
        • If ARR results are not diagnostic and hypertension can be controlled with relatively noninterfering antihypertensives, withdrawal of other potentially interfering medications (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, renin inhibitors, dihydropyridine calcium channel antagonists, β-blockers, central α-2 agonists and non-steroidal anti-inflammatory drugs) for at least 2 weeks prior to a repeat ARR is recommended.
        • While acute fluctuations in dietary sodium are reported to not affect the diagnostic accuracy of the ARR, patients should be informed to liberalize salt intake leading up to the test to ensure accurate results.
    • Sex-hormone producing adrenal tumours are rare and typically present with concomitant clinical symptoms (i.e., feminization or virilisation) and therefore systematic screening may not be warranted
    • Confirmatory hormonal testing is recommended for all positive screening tests to limit false positive results and unnecessary surgeries
• Imaging
  • Unenhanced CT is initial test to rule in adenoma
    • Adenomas typically contain a greater proportion of intracellular fat in comparison to malignant incidentalomas. Therefore, in CT densitometry, a cut-off of <10 HU of a region of interest over a mass increases the likelihood of adenoma
    • Unfortunately, lipid-poor adenomas represent up to 30% of all adenomas and may be indistinguishable from malignancy on unenhanced CT
    • If unenhanced CT is indeterminate, obtain contrast enhanced CT with washouts at 10-15 minutes which has excellent sensitivity and specificity in differentiating between adenomas and nonadenomatous incidentalomas
  • Myelolipoma, cysts and hemorrhages have distinct features on imaging
  • Characteristics of pheochromocytoma and malignant processes include (5):
    1. Size (>3 cm)
    2. Heterogenous texture
    3. Increased vascularity
    4. Attenuation of >10 HU on unenhanced CT
    5. Decreased contrast washout at 10 to 15 minutes
  • Chemical-shift MRI, like unenhanced CT, uses the lipid-rich property of most adenomas to differentiate benign from malignant. However, if an adrenal incidentaloma is indeterminate on unenhanced CT, chemical-shift MRI may not provide additional information and should be deferred in favour of contrast CT with washouts
  • 2-[18F] FDG-PET scan can be useful in detecting metastasis in patients with a history of malignancy, as metabolically-active lesions typically have increased uptake of FDG versus benign lesions.
  • Metaiodobenzylguanidine (MIBG) scintiscan can be useful in assessing patients with suspected pheochromocytoma
• Other
  • Biopsy is currently NOT recommended for the routine workup of adrenal incidentaloma. Its findings rarely alter treatment, except in patients with potential metastases or infectious processes. Often, clinical, hormonal and radiologic findings can effectively direct treatment. It is also associated with relatively rare, but significant, complications;  pheochromocytoma must always be ruled out before biopsy is undertaken to avoid potentially life-threatening hemorrhage and hypertensive crisis

Indications for surgery

1. Size ≥4.0 cm
   • Most adrenocortical carcinomas are >4cm in size
   • Radiologically benign masses >4 cm may be followed in patients who are not prime candidates for surgery
2. Size increases ≥0.5-1.0 cm during follow-up
3. Imaging suspicious of malignancy or pheochromocytoma, regardless of size
4. Adrenal hyperfunction

• • Some patients with primary aldosteronism may be managed medically, especially if they are poor surgical candidates
  • Clinically silent adrenal hyperfunction is an area of debate.
    • Due to the potentially life-threatening complications, it is accepted that any lesions exhibiting silent pheochromocytoma, an adrenal incidentaloma with hormonal and radiologic signs of pheochromocytoma but without clinical symptoms, should be surgically removed after adequate adrenergic blockade
    • Surgery may be elected for younger patients with subclinical Cushing syndrome or those with new onset, medically resistant or deteriorating disease attributable to cortisol excess. The remainder should be admitted to follow-up and recommended for surgery if they develop clinical signs of Cushing’s syndrome.
• Laparoscopic adrenalectomy should be the gold standard for the surgical removal of adrenal masses [Campbell’s suggests that adrenal cancer should not be done laparoscopically]

Follow-up protocol

• Myelolipomas, hemorrhages, cysts do not necessarily require further evaluation
• Non-functioning adenomas, typically < 4 cm, and masses not deemed resectable at initial diagnosis should undergo clinical, hormonal, and radiological surveillance. Currently, there is no consensus on the proper methodology for follow-up. Surveillance proposed in the guidelines:
  • Annual clinical and hormonal testing for up to 4 years
    • There is no agreement on the best mechanism and frequency for hormonal follow-up. However, it should include the same screening tests used at primary evaluation
  • Radiographic assessments (depends on lesion characteristics +/- size)
    • Benign appearing masses
      • <1 cm, consider no further follow-up or enrolment in a clinical trial
      • 1-2cm, first follow-up scan at 12 months if clinical picture warrants
      • 2-4cm, first follow-up scan at 12 months
    • Radiologically suspicious lesions not initially removed
      • Any size, first follow-up scan should be at 3-6 months
    • Further imaging follow-up should be directed by clinical judgment. Consider 1-3 assessments with the first 2 years of diagnosis.
  • Patients with tumours that remain stable on imaging and annual hormonal evaluation may be considered for discharge from follow-up after 4 years